This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is gene ontology?
Gene ontology (GO) is an initiative to provide a shared vocabulary and a body of knowledge about a gene with respect to 3 domains: Molecular Function, Cellular Component, and Biological Process. [1,2]
Molecular Function
This domain describes activities performed by the gene products at the molecular level such as 'catalysis' or 'transport'. [1]
Cellular Component
This domain describes where the gene products function relative to cellular anatomy and structures. [1]
Biological Process
This domain describes the broader biological accomplishments of the gene products such as 'DNA repair' or 'signal transduction'. [1]
Molecular Function
This domain describes activities performed by the gene products at the molecular level such as 'catalysis' or 'transport'. [1]
Cellular Component
This domain describes where the gene products function relative to cellular anatomy and structures. [1]
Biological Process
This domain describes the broader biological accomplishments of the gene products such as 'DNA repair' or 'signal transduction'. [1]
GO terms of StAR
GO, AMIGO, and QuickGO are common gene ontology databases used by scientists. When searching for StAR within these databases, GO returned no specific gene ontology tags, however, AMIGO and QuickGO returned the following ontology classes:
Molecular Function
cholesterol binding cholesterol transport activity protein binding lipid binding |
Cellular Component
mitochondrion mitochondrial intermembrane space cytosol |
Biological Process
cholesterol transport steroid biosynthetic process estrogen biosynthetic process bile acid biosynthetic process |
Cellular Component
StAR is mainly localized in the mitochondria, commonly referred to as the "powerhouse of the cell", where it is involved with transport from the outer mitochondrial membrane to the inner mitochondrial membrane. [3] The figure to the right depicts the main localization of StAR.
Molecular Function
The molecular function of StAR in relation to PCOS is cholesterol binding and transport activity. In 2007, StAR was identified as a "novel mitochondrial cholesterol transporter". [3] Cholesterol is an insoluble molecule and a vital component of cellular membranes which makes the transport activity of StAR crucial within the cell. [3] The figure below comes from the 2007 article where StAR was identified; the figure depicts the trafficking of cholesterol, most importantly, how StAR transports cholesterol from the other mitochondrial membrane to the inner mitochondrial membrane.
Biological Process
StAR plays a key role in steroid hormone synthesis by transporting cholesterol within the mitochondria where it is then cleaved into pregnenolone. [4] The conversion of cholesterol to pregnenolone is the first step in the synthesis of androgens, the steroids that produce 'male' characteristics in humans. [5,6] The figure below highlights the androgen synthesis pathway following the conversion of cholesterol to pregnenolone.
Conclusion
Gene ontology is crucial in uncovering what genes may be involved with biological processes related to diseases of interest. From there, we can observe what molecular functions and cellular components are involved with genes these genes which can elucidate future routes of study. In regards to PCOS, once researchers found it was derived from excess androgen presence, StAR was identified as a candidate gene as a key player in steroidogenesis.
References
[1] Gene ontology overview. Retrieved March 13, 2019 from http://geneontology.org/docs/ontology-documentation/
[2] Gene ontology. Retrieved March 13, 2019 from https://www.nature.com/subjects/gene-ontology
[3] Miller, W. L. (2007). Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochimica et Biophysica Acta (BBA). 1771(6):663-676.
[4] UniProtKB - P49675 (STAR_HUMAN). Retrieved March 14, 2019 from https://www.uniprot.org/uniprot/P49675
[5] Panda, P. K. et al. (2016). Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS. Genome Data. 8:52-60.
[6] Androgen deficiency in men. Retrieved March 14, 2019 from https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/androgen-deficiency-in-men
[1] Gene ontology overview. Retrieved March 13, 2019 from http://geneontology.org/docs/ontology-documentation/
[2] Gene ontology. Retrieved March 13, 2019 from https://www.nature.com/subjects/gene-ontology
[3] Miller, W. L. (2007). Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochimica et Biophysica Acta (BBA). 1771(6):663-676.
[4] UniProtKB - P49675 (STAR_HUMAN). Retrieved March 14, 2019 from https://www.uniprot.org/uniprot/P49675
[5] Panda, P. K. et al. (2016). Genetics of PCOS: A systematic bioinformatics approach to unveil the proteins responsible for PCOS. Genome Data. 8:52-60.
[6] Androgen deficiency in men. Retrieved March 14, 2019 from https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/androgen-deficiency-in-men
Header image: https://wallpapercave.com/scientific-dna-wallpapers-2016